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July 20, 2010BloodOpen Access

Differentially regulated GPVI ectodomain shedding by multiple platelet–expressed proteinases

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Population

Newly generated mice with a megakaryocyte-specific ADAM10 deficiency, Adam17 mice lacking functional ADAM17…

Design

Preclinical

Authors

MBMarkus BenderUniversitätsklinikum WürzburgSHSebastian HofmannJohannes Kepler University of LinzDSDavid StegnerUniversity of Würzburg

Discussion

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Implication

Challenges single-enzyme GPVI targeting for antithrombosis; leaves open the therapeutic role of additional platelet sheddases.

Structured PICO

P
Population
Newly generated mice with a megakaryocyte-specific ADAM10 deficiency, Adam17(ex/ex) mice lacking functional ADAM17, and ADAM10/ADAM17 double-deficient platelets
I
Intervention
In vitro stimuli and in vivo anti-GPVI antibody (JAQ1) administration
O
Outcome
GPVI ectodomain shedding/cleavagesurrogate

GPVI ectodomain shedding is mediated by multiple differentially regulated platelet-expressed proteinases, including ADAM10, ADAM17, and at least one other unidentified enzyme, which has implications for antithrombotic therapy targeting GPVI.

Cite This Study

Bender et al. (2010) studied this question.

synapsesocial.com/papers/6a83a4a36eaad3b729ee75c2https://doi.org/10.1182/blood-2010-06-289108
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Also Consider

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  4. 4ADAM17 Activity and Other Mechanisms of Soluble L-selectin Production during Death Receptor-Induced Leukocyte Apoptosis2010 · 51 citations
  5. 5Constitutive and regulated α-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease1999 · 1,137 citations